Nav: Home

Modern alchemists are making chemistry greener

June 14, 2018

Ancient alchemists tried to turn lead and other common metals into gold and platinum. Modern chemists in Paul Chirik's lab at Princeton are transforming reactions that have depended on environmentally unfriendly precious metals, finding cheaper and greener alternatives to replace platinum, rhodium and other precious metals in drug production and other reactions.

They have found a revolutionary approach that uses cobalt and methanol to produce an epilepsy drug that previously required rhodium and dichloromethane, a toxic solvent. Their new reaction works faster and more cheaply, and it likely has a much smaller environmental impact, said Chirik, the Edwards S. Sanford Professor of Chemistry. "This highlights an important principle in green chemistry -- that the more environmental solution can also be the preferred one chemically," he said. The research was published in the journal Science on May 25.

"Pharmaceutical discovery and process involve all sorts of exotic elements," Chirik said. "We started this program maybe 10 years ago, and it was really motivated by cost. Metals like rhodium and platinum are really expensive, but as the work has evolved, we realized that there's a lot more to it than simply pricing. ... There are huge environmental concerns, if you think about digging up platinum out of the ground. Typically, you have to go about a mile deep and move 10 tons of earth. That has a massive carbon dioxide footprint."

Chirik and his research team partnered with chemists from Merck & Co., Inc., to find more environmentally friendly ways to create the materials needed for modern drug chemistry. The collaboration has been enabled by the National Science Foundation's Grant Opportunities for Academic Liaison with Industry (GOALI) program. 

One tricky aspect is that many molecules have right- and left-handed forms that react differently, with sometimes dangerous consequences. The Food and Drug Administration has strict requirements to make sure medications have only one "hand" at a time, known as single-enantiomer drugs.

"Chemists are challenged to discover methods to synthesize only one hand of drug molecules rather than synthesize both and then separate," said Chirik. "Metal catalysts, historically based on precious metals like rhodium, have been tasked with solving this challenge. Our paper demonstrates that a more Earth-abundant metal, cobalt, can be used to synthesize the epilepsy medication Keppra as just one hand."

Five years ago, researchers in Chirik's lab demonstrated that cobalt could make single-enantiomer organic molecules, but only using relatively simple and not medicinally active compounds -- and using toxic solvents.

"We were inspired to push our demonstration of principle into real-world examples and demonstrate that cobalt could outperform precious metals and work under more environmentally compatible conditions," he said. They found that their new cobalt-based technique is faster and more selective than the patented rhodium approach.

"Our paper demonstrates a rare case where an Earth-abundant transition metal can surpass the performance of a precious metal in the synthesis of single-enantiomer drugs," he said. "What we're starting to transition to is that the Earth-abundant catalysts not only replace the precious metal ones, but they offer distinct advantages, whether it's new chemistry that no one's ever seen before or it's improved reactivity or reduced environmental footprint."

Not only are base metals cheaper and much environmentally friendlier than rare metals, but the new technique operates in methanol, which is much greener than the chlorinated solvents that rhodium requires.

"The manufacture of drug molecules, because of their complexity, is one of the most wasteful processes in the chemical industry," said Chirik. "The majority of the waste generated is from the solvent used to conduct the reaction. The patented route to the drug relies on dichloromethane, one of the least environmentally friendly organic solvents. Our work demonstrates that Earth-abundant catalysts not only operate in methanol, a green solvent, but also perform optimally in this medium.

"This is a transformative breakthrough for Earth-abundant metal catalysts, as these historically have not been as robust as precious metals. Our work demonstrates that both the metal and the solvent medium can be more environmentally compatible."

Methanol is a common solvent for one-handed chemistry using precious metals, but this is the first time it has been shown to be useful in a cobalt system, noted Max Friedfeld, the first author on the paper and a former graduate student in Chirik's lab.

Cobalt's affinity for green solvents came as a surprise, said Chirik. "For a decade, catalysts based on Earth-abundant metals like iron and cobalt required very dry and pure conditions, meaning the catalysts themselves were very fragile. By operating in methanol, not only is the environmental profile of the reaction improved, but the catalysts are much easier to use and handle. This means that cobalt should be able to compete or even outperform precious metals in many applications that extend beyond hydrogenation."

The collaboration with Merck was key to making these discoveries, noted the researchers.

Chirik said: "This is a great example of an academic-industrial collaboration and highlights how the very fundamental -- how do electrons flow differently in cobalt versus rhodium? -- can inform the applied -- how to make an important medicine in a more sustainable way. I think it is safe to say that we would not have discovered this breakthrough had the two groups at Merck and Princeton acted on their own."

The key was volume, said Michael Shevlin, an associate principal scientist at the Catalysis Laboratory in the Department of Process Research & Development at Merck & Co., Inc., and a co-author on the paper.

"Instead of trying just a few experiments to test a hypothesis, we can quickly set up large arrays of experiments that cover orders of magnitude more chemical space," Shevlin said. "The synergy is tremendous; scientists like Max Friedfeld and [co-author and graduate student] Aaron Zhong can conduct hundreds of experiments in our lab, and then take the most interesting results back to Princeton to study in detail. What they learn there then informs the next round of experimentation here."

Chirik's lab focuses on "homogenous catalysis," the term for reactions using materials that have been dissolved in industrial solvents.

"Homogenous catalysis is usually the realm of these precious metals, the ones at the bottom of the periodic table," Chirik said. "Because of their position on the periodic table, they tend to go by very predictable electron changes -- two at a time -- and that's why you can make jewelry out of these elements, because they don't oxidize, they don't interact with oxygen. So when you go to the Earth-abundant elements, usually the ones on the first row of the periodic table, the electronic structure -- how the electrons move in the element -- changes, and so you start getting one-electron chemistry, and that's why you see things like rust for these elements.

Chirik's approach proposes a radical shift for the whole field, said Vy Dong, a chemistry professor at the University of California-Irvine who was not involved in the research. "Traditional chemistry happens through what they call two-electron oxidations, and Paul's happens through one-electron oxidation," she said. "That doesn't sound like a big difference, but that's a dramatic difference for a chemist. That's what we care about -- how things work at the level of electrons and atoms. When you're talking about a pathway that happens via half of the electrons that you'd normally expect, it's a big deal. ... That's why this work is really exciting. You can imagine, once we break free from that mold, you can start to apply it to other things, too."

"We're working in an area of the periodic table where people haven't, for a long time, so there's a huge wealth of new fundamental chemistry," said Chirik. "By learning how to control this electron flow, the world is open to us."
-end-
The paper, Cobalt-catalyzed asymmetric hydrogenation of enamides enabled by single-electron reduction, by Max Friedfeld, Hongyu Zhong, Rebecca Ruck, Michael Shevlin and Paul Chirik, was supported by two grants from the National Science Foundation: a Grant Opportunities for Academic Liaison with Industry (GOALI) grant shared between Princeton and Merck (CHE-1265988) and a graduate research fellowship for Friedfeld (DGE-1148900). DOI: 10.1126/science.aar6117

Princeton University

Related Chemistry Articles:

The chemistry of olive oil (video)
Whether you have it with bread or use it to cook, olive oil is awesome.
With more light, chemistry speeds up
Light initiates many chemical reactions. Experiments at the Laser Centre of the Institute of Physical Chemistry of the Polish Academy of Sciences and the University of Warsaw's Faculty of Physics have for the first time demonstrated that increasing the intensity of illumination some reactions can be significantly faster.
The chemistry of whiskey (video)
Derby Day means it's time to recognize the chemical process of distillation, which makes bourbon possible.
Restoration based on chemistry
Considered the pinnacle of mediaeval painting, the Ghent Altarpiece was painted around 1432 by Jan van Eyck and probably his brother Hubert.
The chemistry of redheads (video)
The thing that sets redheads apart from the crowd is pigmentation.
Scientists discover helium chemistry
The scientists experimentally confirmed and theoretically explained the stability of Na2He.
What might Trump mean for chemistry? (video)
Donald Trump is now the 45th president of the US.
Chemistry on the edge
Defects and jagged surfaces at the edges of nanosized platinum and gold particles are key hot spots for chemical reactivity, researchers confirmed using a unique infrared probe at Berkeley Lab.
Light powers new chemistry for old enzymes
Princeton researchers have developed a method that irradiates biological enzymes with light to expand their highly efficient and selective capacity for catalysis to new chemistry.
Better chemistry through...chemistry
Award-winning UCSB professor Bruce Lipshutz is out to make organic chemistry better for the planet

Related Chemistry Reading:

Chemistry: A Novel (Vintage Contemporaries)
by Weike Wang (Author)

Winner of the PEN/Hemingway Award 

A Washington Post Notable Book

One of the Best Books of the Year: NPR, Entertainment Weekly, Ann Patchett on PBS NewsHour, Minnesota Public Radio, PopSugar, Maris Kreizman, The Morning News

Winner of Ploughshares’ John C. Zacharis Award

Winner of a Whiting Award

A Belletrist Amuse Book

At first glance, the quirky, overworked narrator of Weike Wang’s debut novel seems to be on the cusp of a perfect life: she is studying for a prestigious PhD... View Details


Chemistry: Concepts and Problems: A Self-Teaching Guide
by Clifford C. Houk (Author), Richard Post (Author)

CHEMISTRY SECOND EDITION

The fast, easy way to master the fundamentals of chemistry

Have you ever wondered about the differences between liquids, gases, and solids? Or what actually happens when something burns? What exactly is a solution? An acid? A base? This is chemistry--the composition and structure of substances composing all matter, and how they can be transformed. Whether you are studying chemistry for the first time on your own, want to refresh your memory for a test, or need a little help for a course, this concise, interactive guide gives you a fresh... View Details


Chemistry (Quick Study Academic)
by Inc. BarCharts (Author)

BarCharts’ best-selling quick reference to chemistry has been updated and expanded in this new edition. With updated content and an additional panel of information, this popular guide is not only an essential companion for students in introductory chemistry courses but also a must-have refresher for students in higher-level courses. Author Mark D. Jackson, PhD, a scientist and university chemistry professor, has a gift for making the complicated subject of chemistry interesting and easy to understand―without the fluff. In this new edition, you will find more coverage of the subject,... View Details


Chemistry Essentials For Dummies
by John T. Moore (Author)

Whether studying chemistry as part of a degree requirement or as part of a core curriculum, students will find Chemistry Essentials For Dummies to be an invaluable quick reference guide to the fundamentals of this often challenging course. Chemistry Essentials For Dummies contains content focused on key topics only, with discrete explanations of critical concepts taught in a typical two-semester high school chemistry class or a college level Chemistry I course, from bonds and reactions to acids, bases, and the mole. This guide is also a perfect reference for parents who need to... View Details


Chemistry: An Introduction to General, Organic, and Biological Chemistry (12th Edition) - Standalone book
by Karen C. Timberlake (Author)

For one-semester courses in General, Organic, and Biological Chemistry

 

Show the importance of chemistry in the real world

Chemistry: An Introduction to General, Organic, and Biological Chemistry, Twelfth Edition is the ideal resource for today’s allied health students. Assuming no prior knowledge of chemistry, author Karen Timberlake engages students through her friendly presentation style and reveals connections between the structure and behavior of matter and its role in health and... View Details


Intro to Chemistry Coloring Workbook
by Sonya Writes (Author)

Learn the basics of chemistry through coloring. This book introduces the concepts of:The Periodic table Protons, electrons and neutrons Bohr models Orbitals Diatomic elements Covalent bonds Ionic bonds...and more! View Details


Chemistry: The Central Science (13th Edition)
by Theodore E. Brown (Author), H. Eugene LeMay (Author), Bruce E. Bursten (Author), Catherine Murphy (Author), Patrick Woodward (Author), Matthew E. Stoltzfus (Author)

Chemistry Text, latest edition, required text View Details


Chemistry: A Molecular Approach
by Nivaldo J. Tro (Author)

ALERT: This is a standalone book and does not contain an access code. If you would like to purchase the version that includes the Access Card Package please visit: http://www.amazon.com/dp/0321804716


Chemistry: A Molecular Approach, Third Edition is an innovative, pedagogically driven text that explains challenging concepts in a student-oriented manner.  Nivaldo Tro creates a rigorous and accessible treatment of general chemistry in... View Details


The Cartoon Guide to Chemistry
by Larry Gonick (Author), Craig Criddle (Author)

If you have ever suspected that "heavy water" is the title of a bootleg Pink Floyd album, believed that surface tension is an anxiety disorder, or imagined that a noble gas is the result of a heavy meal at Buckingham Palace, then you need The Cartoon Guide to Chemistry to set you on the road to chemical literacy.

You don't need to be a scientist to grasp these and many other complex ideas, because The Cartoon Guide to Chemistry explains them all: the history and basics of chemistry, atomic theory, combustion, solubility, reaction stoichiometry, the mole, entropy,... View Details


Chemistry Lessons
by Meredith Goldstein (Author)

From advice columnist Meredith Goldstein, a dazzling, romantic, and emotionally resonant YA debut about a teen science whiz in Cambridge, Massachusetts, who tries to crack the chemical equation for lasting love and instead wreaks havoc on herself and the boys in her life.

For seventeen-year-old Maya, the equation for happiness is simple: a dream internship at MIT + two new science nerd friends + a perfect boyfriend = one amazing summer. Then Whit dumps her out of the blue. 
 
Maya is miserable until she discovers that her scientist mother, before she died, was... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Person You Become
Over the course of our lives, we shed parts of our old selves, embrace new ones, and redefine who we are. This hour, TED speakers explore ideas about the experiences that shape the person we become. Guests include aerobatics pilot and public speaker Janine Shepherd, writers Roxane Gay and Taiye Selasi, activist Jackson Bird, and fashion executive Kaustav Dey.
Now Playing: Science for the People

#479 Garden of Marvels (Rebroadcast)
This week we're learning about botany and the colorful science of gardening. Author Ruth Kassinger joins us to discuss her book "A Garden of Marvels: How We Discovered that Flowers Have Sex, Leaves Eat Air, and Other Secrets of the Way Plants Work." And we'll speak to NASA researcher Gioia Massa about her work to solve the technical challenges of gardening in space.